Sudden death due to aortic rupture in New Zealand sheep.

CASE HISTORY: Over a period of 2 months in the spring and early summer of 2021, 13 cases of sudden death in cull ewes due to aortic rupture were diagnosed at a small number of New Zealand abattoirs. CLINICAL FINDINGS: In 12/13 (92%) cases, a large blood clot was present in the thorax, and in one case the blood clot was seen in the tissues dorsal to the heart. There were no obvious signs of external trauma. The pluck (heart and lungs) or fixed aorta was submitted for histological examination in seven cases and in all of these, a tear in the aorta was found. Comparing the microscopic appearance of the proximal aorta in these seven cases to three clinically normal ewes from unaffected farms, the aortic wall thickness appeared thinner in the case ewes than the unaffected ewes. Subjectively, there was increased collagen in the tunica media in 3/7 and decreased elastin fibres in 5/7 case ewes compared to the control ewes. Further investigations on the index farm (where the first cases originated), found that the mean liver and serum Cu concentrations in 10 similarly aged, clinically normal ewes were within the normal reference range for New Zealand sheep. Similarly, the liver Cu concentrations of the seven case ewes were within the normal reference range. DIAGNOSIS: Aortic rupture due to an unknown aetiology. CLINICAL RELEVANCE: Clinicians should be aware of this condition as a differential diagnosis for sudden death in older sheep and to assist the Ministry for Primary Industries in establishing the extent of this problem in New Zealand.

Prevalence of cardiomyopathy and cardiac mortality in a colony of non-purebred cats in New Zealand.

AIMS: To evaluate the prevalence of subclinical cardiomyopathy and cardiac mortality in a research colony of non-purebred cats, established as a model of the wider cat population in New Zealand. METHODS: All apparently healthy, compliant, non-pregnant, non-neonatal cats in the colony at the Centre for Feline Nutrition (Massey University, Palmerston North, NZ) underwent physical examination and echocardiography using a 4.4-6.2-MHz probe by a board-certified veterinary cardiologist. Cardiac phenotype was classified following current guidelines. Hypertrophic cardiomyopathy (HCM) phenotype was defined as an end-diastolic left ventricular wall thickness ≥ 6 mm. Colony mortality data from February 2012 to February 2022 was reviewed to determine cardiac mortality. RESULTS: Cats (n = 132; 65 females and 67 males) included in the study had a median age of 4.1 (IQR 3.0-8.0) years. Thirty-two (24%) cats had a heart murmur, and three (2%) cats had an arrhythmia. Echocardiography revealed heart disease in 24 (18.2%) cats, including 23 with an HCM phenotype and one with a restrictive cardiomyopathy phenotype. Of the cats with the HCM phenotype, 3/23 had systemic hypertension or hyperthyroidism or both, and these cats were excluded from the final diagnosis of HCM (20/132; 15.2 (95% CI = 9.5-22.4)%).Between 2012 and 2022, 168 colony cats died, with 132 undergoing post-mortem examination. Heart disease was considered the cause of death in 7/132 (5.3%; 95% CI = 2.2-10.6%) cats; five had HCM, one a congenital heart defect, and one myocarditis. The overall prevalence of death related to HCM in the colony during this period was 3.8% (95% CI = 1.2-8.6%). Three cats with HCM and the cat with a congenital heart defect died unexpectedly without prior clinical signs, while congestive heart failure was observed prior to death in two cats with HCM and the cat with myocarditis. Additionally, 30/132 (22.7%) cats had cardiac abnormalities but died for non-cardiac reasons. CONCLUSIONS: Subclinical cardiomyopathy, specifically HCM, was common in cats in the colony. Given that the colony originated as a convenience selection of non-purebred cats in New Zealand, the true prevalence of HCM in the wider New Zealand population is likely to fall within the 95% CI (9.5-22%). The proportion of deaths of colony cats due to HCM was lower (3.8%) supporting the conclusion that subclinical cardiomyopathy may not progress to clinical disease causing death. CLINICAL RELEVANCE: Veterinarians should be aware of the high prevalence of subclinical HCM when treating cats. ABBREVIATIONS: CAM: Systolic anterior motion of the chordae tendineae; CFN: Centre for Feline Nutrition; HCM: Hypertrophic cardiomyopathy; LA/Ao: Left atrial to aortic ratio; LV FS: Left ventricular fractional shortening; LVIDd: Left ventricular internal diameters in end-diastole; LVIDs: Left ventricular internal diameter in end-systole; LVWT: Max Maximum left ventricular wall thickness; SAM: Systolic anterior motion of the mitral valve; 2D: Two-dimensional.

An outbreak of ischaemic teat necrosis in a dairy herd in Taranaki, New Zealand.

CASE HISTORY: In spring 2021, on a seasonally calving, pastorally based, Taranaki dairy farm, 12 first-calving heifers (≤ 30 days post-calving) developed similar dry, red to black, crusting lesions on the medial aspect of the teat udder junction extending down the medial teat. Some cows had multiple teats affected. Treatment was initially unrewarding and did not slow the progression of the disease. Overall, 8/12 cows recovered, and 4/12 cows were culled, with three of the cows culled after a teat sloughed and the fourth after surgical amputation of a teat. Outbreaks of the same condition, on the same farm but affecting fewer animals, occurred in spring 2022 (n = 6) and spring 2023 (n = 3). CLINICAL FINDINGS: An initial scab-like or crusting lesion progressed to resemble a thick eschar consisting of very dry and hard dead tissue. The unaffected areas of the teat felt normal but immediately under the dead tissue, there was a warm, firmer area consistent with an inflammatory reaction. Removing the scab led to profuse bleeding, with no visible bed of granulation underneath the scab. There was no leaking of milk in those cows that lost a teat, and no smell to the lesions themselves. Serology and virology ruled out the involvement of bovine alphaherpesvirus (BoHV-2) bovine gammaherpesvirus (BoHV-4), orthopoxviruses (cowpox) and parapoxviruses (pseudocowpox). Histopathology of an affected and surgically amputated teat showed multifocal erosion and ulceration of the epidermis, covered by a thick serocellular crust. In areas of ulceration, there were numerous neutrophils, and the dermis was expanded by granulation tissue with variable numbers of neutrophils, eosinophils, and lymphocytes around small blood vessels. DIAGNOSIS: Based on the similarity of the history, presentation, and histopathological changes to those described for a novel disease reported in the UK, a diagnosis of ischaemic teat necrosis (ITN) was made. CLINICAL RELEVANCE: If ITN is an emerging condition in New Zealand and becomes as prevalent as it has in the UK, clinicians will be confronted with a significant new welfare problem in dairy cows. Anecdotally, there have been reports of other ITN outbreaks in New Zealand, and the Ministry for Primary Industries would be interested in collating reports from other New Zealand veterinarians.

Pharmacokinetics and effect on renal function and average daily gain in lambs after castration and tail docking, of firocoxib and meloxicam.

AIMS: To evaluate and compare the pharmacokinetics of IM and oral firocoxib, and IM meloxicam, and detect their effect on renal function and average daily gain (ADG) in lambs undergoing tail docking and castration. METHODS: Seventy-five male Romney lambs, aged 3-6 weeks, were randomised into five treatment groups (n = 15 per group): IM firocoxib (1 mg/kg); oral firocoxib (1 mg/kg); IM meloxicam (1 mg/kg); normal saline (approximately 2 mL, oral); or sham. Following the treatment administration, hot-iron tail docking and rubber ring castration were performed in all groups except the sham group, which did not undergo the procedures, but the animals were handled in the same manner as castrated and tail docked lambs. Blood samples were collected before and 1, 2, 4, 6, 8, 24, 48, 72, 96 and 120 hours after treatment administration, and drug concentrations in plasma were quantified by liquid chromatography and mass spectrometry. Plasma urea and creatinine concentrations were determined at a commercial laboratory. Lamb body weights were recorded before and 2, 4 and 8 weeks after tail docking and castration. The pharmacokinetic analysis was carried out using a non-compartmental approach. Between-group and between-time-point differences were compared using mixed model analyses. RESULTS: There was no evidence for a difference in plasma elimination half-life between firocoxib given IM (LSM 18.6 (SE 1.4) hours), firocoxib given orally (LSM 18.2 (SE 1.4) hours), and meloxicam given IM (LSM 17. 0 (SE 1.4) hours). Firocoxib (IM) had a significantly greater volume of distribution (LSM 3.7 (SE 0.2) L/kg) than IM meloxicam (LSM 0.2 (SE 0.2) L/kg). Lambs in the meloxicam group had higher (p < 0.05) plasma urea and creatinine concentrations than those in the firocoxib, saline and sham groups. Lambs' ADG was decreased (p < 0.01) compared to the other treatment groups in the 0-2 week period following meloxicam administration. CONCLUSIONS AND CLINICAL RELEVANCE: Both formulations of firocoxib had a long plasma elimination half-life and large volume of distribution. There was a transient reduction in ADG in the meloxicam group, possibly due to mild renal toxicity. Comparative studies on dose-response effects of firocoxib and meloxicam in lambs following the procedures are required.Abbreviations: ADG: Average daily gain; Cmax: Maximum concentration; COX: Cyclooxygenase; LOD: Limit of detection; NSAID: Non-steroidal anti-inflammatory drugs; CL: Plasma clearance; T1/2el: Plasma elimination half-life; Tmax: Time to achieve Cmax; Vd: Volume of distribution.

Ulnar diaphyseal stress injuries: a case series.

AIM: To describe the demographics, clinical context, imaging findings, and management of a case series of ulnar diaphyseal stress injuries (UDSIs) and propose a unifying mechanism for these injuries based on the imaging findings. MATERIALS AND METHODS: Seven patients from University of Florida College of Medicine (seven total injuries; mean age: 19 ± 4.4 years; three females, four males) with available clinic and imaging data and without predisposing comorbidities were included in this retrospective study. The age, gender, laterality of injury with respect to the dominant hand, attributed inciting activity, imaging method, presence and location of stress injury findings, as well as the subsequent management were analysed. RESULTS: All patients were in the second or third decade of life and there was a slight male predominance to the case series (57%). All UDSIs in this series were unilateral. Fifty-seven percent of injuries involved the dominant ulna and all involved the ulnar diaphysis along the proximal-mid junction, mid diaphysis or mid-distal junction. All injuries involved portion of the ulnar origin of the flexor digitorum profundus (FDP). All patients were managed conservatively. CONCLUSION: UDSIs are uncommon and associated with a broad range of occupational or sports-related activities. All cases in this series involved the ulnar origin of the FDP suggesting an important role for the forces exerted by this muscular attachment on the underlying bone with regard to the development of UDSIs.

Clinician perspectives on having point of care tests made available to them during out of hours home visiting.

BACKGROUND: Little is known about clinicians' perspectives on the use of point of care (POC) tests in assessment of acute illness during primary care out of hours (OOH) care. During a service improvement project, POC tests (including creatinine, electrolytes, haemoglobin and lactate) were made available to clinicians undertaking OOH home visits, with the clinicians allowed absolute discretion about when and whether they used them. METHOD: To explore clinicians' perspectives on having POC tests available during OOH home visits, we undertook a qualitative study with clinicians working in Oxfordshire OOH home visiting teams. We conducted 19 Semi-structured interviews with clinicians working in OOH, including those who had and had not used the POC tests available to them. To explore evolving perspectives over time, including experience and exposure to POC tests, we offered clinicians the opportunity to be interviewed twice throughout the study period. Our sample included 7 GPs (4 interviewed once, 3 interviewed twice - earlier and later during the study), 6 emergency practitioners (EPs) including advanced nurse practitioners and paramedics, 1 Healthcare Assistant, and 2 ambulatory care physicians. Interviews were audio-recorded, transcribed verbatim and analysed thematically. RESULTS: The clinicians reflected on their decision-making to use (or not use) POC tests, including considering which clinical scenarios were "appropriate" and balancing the resources and time taken to do POC tests against what were perceived as likely benefits. The challenges of using the equipment in patients' homes was a potential barrier, though could become easier with familiarity and experience. Clinicians who had used POC tests described benefits, including planning onward care trajectories, and facilitating communication, both between professionals and with patients and their families. CONCLUSION: Clinicians described a discriminatory approach to using POC tests, considering carefully in which situations they were likely to add value to clinical decision-making.

An epidemiological investigation of an idiopathic myopathy in hunting dogs in New Zealand.

AIM: To conduct an epidemiological investigation of an idiopathic myopathy, known as "Go Slow" (GSM), which was initially recognised in dogs used for pig hunting. A secondary aim was to describe the hunting activities, diet and health of dogs used for pig hunting in New Zealand. METHODS: A retrospective cohort study was conducted between June 2014-June 2017. Cases of GSM in dogs were diagnosed by veterinarians using a combination of clinical history, physical examination findings, serum biochemistry and/or skeletal muscle histology. A telephone interview was conducted with the owner or primary veterinarian to provide information regarding the dog's diet and exercise over the 7 days preceding the onset of clinical signs. In August 2015, a separate online survey of owners of dogs used for pig hunting was conducted to characterise the normal hunting activities, diet and health of these dogs. RESULTS: A total of 86 cases of GSM were recruited, of which 58 (67%) were pig hunting dogs, 16 (19%) pet dogs and 12 (14%) working farm dogs. Cases were most commonly reported in the upper North Island, and 65 (76 (95% CI=67-85)%) were from the Northland region. Processed commercial dog food had been fed to 93 (95% CI=88-98)% of affected dogs. Ingestion of raw, frozen or cooked wild pig in the preceding week was reported for 76 (88 (95% CI=82-95)%) dogs with the myopathy. In the survey of owners of healthy pig hunting dogs, 203 eligible responses were received; pig hunting was reported to most commonly occur in Northland (20.2%), Waikato (22.3%) and Bay of Plenty (23.2%) regions. Commercial dog food was fed to 172 (85 (95% CI=80-90)%) of the dogs included in this survey, and 55 (27 (95% CI=20-33)%) had eaten wild pig in the preceding week. The most common reported health problem in pig hunting dogs was traumatic wounds. CONCLUSIONS: Cases of GSM were most commonly recognised in dogs used for pig hunting, but also occurred in pet and working farm dogs. The disease was most frequently reported in the upper North Island of New Zealand and ingestion of wild pig was a consistent feature in cases of this myopathy. CLINICAL RELEVANCE: To minimise the risk of dogs developing this myopathy, it would seem prudent to avoid feeding any tissues from wild pigs to dogs in areas where the disease is known to occur.

A novel combined glucocorticoid-mineralocorticoid receptor selective modulator markedly prevents weight gain and fat mass expansion in mice fed a high-fat diet.

BACKGROUND: We have previously shown that antagonism of the mineralocorticoid receptor (MR) results in a potent antiadipogenic activity, in vitro and in vivo. Excessive glucocorticoid exposure is associated with obesity and related disorders in humans and mice. METHODS: In this study, responses to a novel combined glucocorticoid receptor (GR)/MR antagonist were investigated in a model of diet-induced obesity. Female 10-week-old C57BL/6J mice were fed with normal chow or a high-fat diet (HFD) for 9 weeks. Mice fed a HFD were concomitantly treated for 9 weeks with the GR antagonist mifepristone (80 mg kg(-1) per day) or the novel combined GR/MR antagonist CORT118335 (80 mg kg(-1) per day). Male, juvenile 6-week-old C57BL/6J mice fed HFD were treated with CORT118335 for 4 weeks. RESULTS: Mice fed a HFD showed a significant increase in total body weight and white fat mass, with impaired glucose tolerance and increased fat infiltration in livers. Interestingly, only CORT118335 completely prevented the HFD-induced weight gain and white fat deposition, whereas mifepristone showed no effect on body weight and modestly increased subcutaneous fat mass. Importantly, food intake was not affected by either treatment, and CORT118335 dramatically increased PGC-1α protein expression in adipose tissue, without any effect on UCP1. Both CORT118335 and mifepristone produced metabolic benefit, improving glucose tolerance, increasing adiponectin plasma levels, decreasing leptin and reducing mean adipocyte size. When tested in vitro, CORT118335 markedly reduced 3T3-L1 differentiation and reversed MR-mediated pro-adipogenic effects of aldosterone; differently, GR-mediated effects of dexamethasone were not antagonized by CORT118335, suggesting that it mostly acts as an antagonist of MR in cultured preadipocytes. CONCLUSIONS: Combined GR/MR pharmacological antagonism markedly reduced HFD-driven weight gain and fat mass expansion in mice through the increase in adipose PGC-1α, suggesting that both receptors represent strategic therapeutic targets to fight obesity. The effects of CORT118335 in adipocytes seem predominantly mediated by MR antagonism.

First report and histological features of Chlamydia pecorum encephalitis in calves in New Zealand.

CASE HISTORY: Between September and October 2013, 40 of 150 crossbred Friesian dairy calves on a farm in the Manawatu region of New Zealand developed neurological signs when between 1 and 3 months of age. Calves were grazed in multiple mobs and calves from each mob were affected. A variable response was observed to initial treatment with thiamine, fluoroquinolone antibiotics and non-steroidal anti-inflammatory drugs. CLINICAL AND PATHOLOGICAL FINDINGS: Affected calves exhibited a range of neurological signs that included generalised depression, hind limb ataxia with a stiff gait, and knuckling of the fetlocks. In advanced cases, calves became recumbent with opisthotonous. Over a 4-week period, 13 calves died or were subject to euthanasia and a thorough necropsy was performed on three of these calves. Necropsy findings included fibrinous peritonitis, pleuritis and pericarditis, with no gross abnormalities visible in the brain or joints. Histology of the brain was possible in seven of the affected calves, with lesions ranging from lymphocytic and histiocytic vasculitis and meningoencephalitis, to extensive thrombosis and neutrophilic inflammation. Immunohistochemistry using an anti-chlamydial lipopolysaccharide antibody revealed positive immuno-staining in all seven cases, with no brain samples exhibiting immunostaining for Histophilus somni. DNA was extracted from a sample of fresh brain from one case and chlamydial DNA sequences were amplified by PCR and found to be identical to Chlamydia pecorum. PCR was also performed on formalin-fixed brain tissue from three of the other cases, but no chlamydial DNA was amplified. DIAGNOSIS: Chlamydia pecorum meningoencephalomyelitis (sporadic bovine encephalomyelitis). CLINICAL RELEVANCE: This is the first time that C. pecorum has been confirmed as a cause of clinical disease in New Zealand. Practitioners should be aware of this disease as a differential in calves with neurological signs, and submit samples of formalin-fixed brain as well as fresh brain to enable confirmation of suspected cases using PCR analysis. Furthermore, these cases illustrate that the histological lesions in the brains of calves with C. pecorum are more variable than previously reported, and pathologists should be aware that histological features may overlap with those traditionally ascribed to other organisms, such as H. somni.

Measuring and monitoring ICP in Neurocritical Care: results from a national practice survey.

INTRODUCTION: The use of intracranial pressure (ICP) monitors is nearly synonymous with Neurocritical Care. Recent studies in nursing literature have report high levels of practice variance associated with ICP monitoring and treatment. There are no recent practice surveys to describe how critical care physicians and nurses who are familiar with ICP management provide care to their patients. METHODS: A short survey was developed and disseminated electronically to the members of the Neurocritical Care Society. RESULTS: The summary from 241 professionals provides evidence that there is significant practice variation associated with ICP monitoring and management. CONCLUSION: The results highlight the need to develop standardized approaches to measuring, monitoring, recording, and treating ICP.

Distinct neuropsychological profiles correspond to distribution of cortical thinning in inherited prion disease caused by insertional mutation.

BACKGROUND: The human prion diseases are a group of universally fatal neurodegenerative disorders associated with the auto-catalytic misfolding of the normal cell surface prion protein (PrP). Mutations causative of inherited human prion disease (IPD) include an insertion of six additional octapeptide repeats (6-OPRI) and a missense mutation (P102L) with large families segregating for each mutation residing in southern England. Here we report for the first time the neuropsychological and clinical assessments in these two groups. METHOD: The cognitive profiles addressing all major domains were obtained for 26 patients (18 6-OPRI, 8 P102L) and the cortical thickness determined using 1.5T MRI in a subset of 10 (six 6-OPRI, four P102L). RESULTS: The cognitive profiles were different in patients with the two mutations in the symptomatic phase of the disease. The 6-OPRI group had lower premorbid optimal levels of functioning (assessed on the NART) than the P102L group. In the symptomatic phase of the disease the 6-OPRI patients had significantly more executive dysfunction than the P102L group and were more impaired on tests of perception and nominal functions. There was anecdotal evidence of low premorbid social performance in the 6-OPRI but not P102L patients. Cortical thinning distribution correlated with the neuropsychological profile in the 6-OPRI group principally involving the parietal, occipital and posterior frontal regions. The small number of patients in the P102L group precluded statistical comparison between the groups. CONCLUSIONS: The 6-OPRI patients had more widespread and severe cognitive dysfunction than the P102L group and this correlated with cortical thinning distribution.

Is Pathological Exam for Disorders of the Appendix Testis Necessary?

Testicular appendages are remnants of embryologic structures commonly encountered during pediatric operations. The literature is vague on the management of incidentally discovered testicular appendages found intraoperatively. We performed a retrospective review of 93 pediatric patients who were found to have an incidental testicular appendage during inguinal hernia repair, cryptorchidism, or testicular torsion cases from December 2017 to June 2020. 100% of the incidental testicular appendage pathology results were benign. All of the specimens were 1.0 cm or less in their largest dimension. Removal of these specimens is considered the standard of care at our institution to help prevent torsion of the testicular appendage, which is one of the leading causes of acute scrotum in children. The authors of this study argue that pathological analysis is unnecessary and may result in excessive use of resources without proven benefit.

Alloreactive cytotoxic T lymphocytes recognize epitopes determined by both the alpha helices and beta sheets of the class I peptide binding site.

A chimeric class I glycoprotein was created to investigate the functional contribution of the alpha helices and the beta-pleated sheets in forming the antigen recognition site (ARS) of antigen-presenting molecules. This novel molecule was generated by replacing the DNA sequences encoding the alpha helices of the Ld gene with the corresponding sequences from the Kb gene. Serologic analysis of transfected L cells that expressed the chimeric molecule (Kb alpha Ld beta) revealed that the engineered class I glycoprotein retains two conformational epitopes associated with the alpha helices of Kb, as defined by monoclonal antibodies K10.56 and 28-13-3. These results demonstrate that the alpha helices of Kb can associate with the beta-pleated sheets of Ld to form a stable structure, which is expressed on the cell surface. To address the role of the alpha helices of the ARS in determining T cell crossreactivity, alloreactive cytotoxic T lymphocytes (CTL) were used to analyze L cells expressing Kb alpha Ld beta. CTL raised against Kb or Ld as alloantigens showed little, if any, ability to lyse L cells expressing Kb alpha Ld beta. Thus, alloreactive CTL did not recognize structures determined by the alpha helices alone or by the beta sheets of the ARS alone. However, bulk and cloned alloreactive CTL that were generated against the mutant Kb glycoprotein Kbm8 reacted strongly with Kb alpha Ld beta. In addition to the Kb alpha helices, the Kbm8 ARS shares a single polymorphic amino acid at position 24 with Kb alpha Ld beta. Amino acid 24 is located on the beta 2 strand that forms part of the floor of the ARS and has been identified as a component of pocket B in the HLA class I ARS. The substitution of Glu to Ser at this position was shown previously to be the central determinant of the Kbm8 mutant alloantigenicity. The functional significance of this position in determining crossreactivity between bm8 and Kb alpha Ld beta identifies pocket B as a strong anchor for allogenic self-peptides. These findings demonstrate that determinants recognized by CTL on class I alloantigens are formed by interactions involving both the alpha helices and beta sheets of the ARS. These interactions are best explained by the influence of the alpha helices and beta sheets on the peptide-binding properties of these antigen-presenting molecules.

Subgroup J avian leukosis virus neutralizing antibody escape variants contribute to viral persistence in meat-type chickens.

We have previously demonstrated a high incidence of chickens with persistent viremia even in the presence of neutralizing antibodies (V+A+) against the inoculated parental virus in commercial meat-type chickens inoculated at hatch with subgroup J avian leukosis virus (ALV J) field isolates. In this study, we used an ALV J molecular clone, ADOL pR5-4, to determine the role of neutralizing antibody (NAb) escape mutants in maintaining a high incidence of viral persistence, namely, V+A+ infection profile in commercial meat-type chickens. Chickens were housed as a flock in a pen or housed in isolation in solitary Horsfall-Bauer units for testing for NAb escape variants. The emergence of NAb escape variants was evaluated by sequential autologous virus neutralization (VN) (between virus and antibody from the same sampling period) and heterologous VN (between virus and antibody from preceding and succeeding sampling periods). Sequential virus isolates and corresponding antisera from 18 chickens were examined by VN matrix. In all chickens, autologous virus isolates were not neutralized by corresponding antisera. However, some of these resilient autologous virus isolates were neutralized by antibodies from subsequent sampling intervals. Nucleotide sequence analysis of consecutive isolates from three individually housed chickens with V+A+ infection profile revealed distinct changes within the envelope region, suggesting viral evolution to escape the host immune response. These results demonstrate that the emergence of antibody escape variants in commercial meat-type chickens contributes to ALV J persistence.

Genetic diversity and phylogeography in two diploid ferns, Asplenium fontanum subsp. fontanum and A. petrarchae subsp. bivalens, in the western Mediterranean.

Asplenium fontanum subsp. fontanum and A. petrarchae subsp. bivalens are diploid rock ferns of limestone outcrops of the western Mediterranean region. Asplenium fontanum subsp. fontanum occurs from Valencia through northeastern Spain to the Alpes-Maritimes and Swiss Jura. Asplenium petrarchae subsp. bivalens occurs only on Majorca, in Valencia and possibly in southern Spain. We analysed allozyme and chloroplast genetic marker diversity in 75 populations of A. fontanum subsp. fontanum and 12 populations of A. petrarchae subsp. bivalens sampled from across their respective ranges. The two species show similar levels of species and population genetic diversity to one another and to other diploid European Asplenium taxa. Both are predominantly outbreeding, as indicated by F(IS) = 0.108 and 0.167 respectively. Substantial between-population differentiation results largely from differentiation between regions. Isolation by distance operates over limited geographic ranges, up to 50 km. In A. fontanum subsp. fontanum, the major geographical differentiation between Valencia and the rest of the taxon range probably represents an ancient range fragmentation. A less pronounced differentiation divides populations in the SW from those in the NE of the range, with evidence for a biogeographic link between the eastern Pyrenees and southeastern France. High diversity in the Pyrenees may either represent ancient population differentiation, or a suture zone. In A. petrarchae subsp. bivalens, populations on Majorca exhibit a subset of the genetic diversity present in Valencia, although the two regions are strongly differentiated by differing allele frequencies. Dispersal from the mainland may have founded Majorcan populations, although a role for in situ island survival cannot be excluded.

Influence of productivity on the stability of real and model ecosystems.

The lengths of food chains within ecosystems have been thought to be limited either by the productivity of the ecosystem or by the resilience of that ecosystem after perturbation. Models based on ecological energetics that follow the form of Lotka-Volterra equations and equations that include material (detritus) recycling show that productivity and resilience are inextricably interrelated. The models were initialized with data from 5-to 10-year studies of actual soil food webs. Estimates indicate that most ecological production worldwide is from ecosystems that are themselves sufficiently productive to recover from minor perturbations.

Retroviral delivery of RNA interference against Marek's disease virus in vivo.

The process of RNA interference (RNAi) has been exploited in cultured chicken cells and in chick embryos to assess the effect of specific gene inhibition on phenotypes related to development and disease. We previously demonstrated that avian leukosis virus-based retroviral vectors are capable of delivering effective RNAi against Marek's disease virus (MDV) in cell culture. In this study, similar RNAi vectors are shown to reduce the replication of MDV in live chickens. Retroviral vectors were introduced into d 0 chick embryos, followed by incubation until hatching. Chicks were challenged with 500 pfu of strain 648A MDV at day of hatch, followed by assays for viremia at 14 d postinfection. Birds were monitored for signs of Marek's disease for 8 wk. A stem-loop PCR assay was developed to measure siRNA expression levels in birds. Delivery of RNAi co-targeting the MDV gB glycoprotein gene and ICP4 transcriptional regulatory gene significantly reduced MDV viremia in vivo, although to lesser extents than were observed in cell culture. Concomitant reductions in disease incidence also were observed, and the extent of this effect depended on the potency of the MDV challenge virus inoculum. Successful modification of phenotypic traits in live birds with retroviral RNAi vectors opens up the possibility that such approaches could be used to alter the expression of candidate genes hypothesized to influence a variety of quantitative traits including disease susceptibility.

Use of test accuracy study design labels in NICE's diagnostic guidance.

BACKGROUND: A variety of study designs are available to evaluate the accuracy of tests, but the terms used to describe these designs seem to lack clarity and standardization. We investigated if this was the case in the diagnostic guidance of the National Institute of Care and Health Excellence (NICE), an influential source of advice on the value of tests. OBJECTIVES: To describe the range of study design terms and labels used to distinguish study designs in NICE Diagnostic Guidance and the underlying evidence reports. METHODS: We carefully examined all NICE Diagnostic Guidance that has been developed from inception in 2011 until 2018 and the corresponding diagnostic assessment reports that summarized the evidence, focusing on guidance where tests were considered for diagnosis. We abstracted labels used to describe study designs and investigated what labels were used when studies were weighted differently because of their design (in terms of validity of evidence), in relevant sections. We made a descriptive analysis to assess the range of labels and also categorized labels by design features. RESULTS: From a total of 36 pieces of guidance, 20 (56%) were eligible and 17 (47%) were included in our analysis. We identified 53 unique design labels, of which 19 (36%) were specific to diagnostic test accuracy designs. These referred to a total of 12 study design features. Labels were used in assigning different weights to studies in seven of the reports (41%) but never in the guidance documents. CONCLUSION: Our study confirms a lack of clarity and standardization of test accuracy study design terms. There seems to be scope to reduce and harmonize the number of terms and still capture the design features that were deemed influential by those compiling the evidence reports. This should help decision makers in quickly identifying subgroups of included studies that should be weighted differently because their designs are more susceptible to bias.

Untargeted metabolic profiling of dogs with a suspected toxic mitochondrial myopathy using liquid chromatography-mass spectrometry.

'Go Slow myopathy' (GSM) is a suspected toxic myopathy in dogs that primarily occurs in the North Island of New Zealand, and affected dogs usually have a history of consuming meat, offal or bones from wild pigs (including previously frozen and/or cooked meat). Previous epidemiological and pathological studies on GSM have demonstrated that changes in mitochondrial structure and function are most likely caused by an environmental toxin that dogs are exposed to through the ingestion of wild pig. The disease has clinical, histological and biochemical similarities to poisoning in people and animals from the plant Ageratina altissima (white snakeroot). Aqueous and lipid extracts were prepared from liver samples of 24 clinically normal dogs and 15 dogs with GSM for untargeted liquid chromatography-mass spectrometry. Group-wise comparisons of mass spectral data revealed 38 features that were significantly different (FDR<0.05) between normal dogs and those with GSM in aqueous extracts, and 316 significantly different features in lipid extracts. No definitive cause of the myopathy was identified, but alkaloids derived from several plant species were among the possible identities of features that were more abundant in liver samples from affected dogs compared to normal dogs. Mass spectral data also revealed that dogs with GSM have reduced hepatic phospholipid and sphingolipid concentrations relative to normal dogs. In addition, affected dogs had changes in the abundance of kynurenic acid, various dicarboxylic acids and N-acetylated branch chain amino acids, suggestive of mitochondrial dysfunction.

Tulip Giant Aneurysm Amputation and "Shingle Clip Cut Clip" Technique for Microsurgical Reconstruction of a Giant Thrombosed Middle Cerebral Artery Aneurysm.

In this video, we present the case of a 61-year-old female who was brought to the emergency department after she had partial complex seizures. Computed tomography and magnetic resonance imaging of the brain revealed a right temporal lobe mass, which was initially thought to be a tumor. The patient was therefore referred to us for further management. The round nature of the lesion raised suspicion for an aneurysm. Computed tomography angiography was performed, followed by a diagnostic conventional cerebral angiogram, and confirmed the presence of a giant thrombosed aneurysm. Giant aneurysms represent 3%-5% of all cerebral aneurysms.1 They are more common in females with a ratio of 2:1 to 3:1.1 They have a high risk of rupture up to 50% in the posterior circulation and 40% in the anterior circulation over 5 years according to the International Study of Unruptured Intracranial Aneurysms Investigators.2,3 Their treatment can be complex and treacherous. Treatment options vary widely from parent artery sacrifice in select cases to clip reconstruction to an array of endovascular approaches such as flow diversion. In some cases a combination of both open and endovascular approaches might be necessary.4-8 In our case, we opted for an open surgical clip reconstruction. A superior temporal artery-middle cerebral artery bypass was attempted to allow for trapping of the aneurysm without risking ischemic complication distal to it. Unfortunately, the patient's vessels were too atherosclerotic to maintain patency. A strategy was then devised, which consisted of cutting the dome of the aneurysm and clearing the distal two thirds of the clot ("tulip technique") and then completing thrombus resection under temporary occlusion. Once clot removal was completed, the aneurysm was clipped using the "shingle clip cut clip" technique (Video 1). The patient's postoperative course was uneventful, and the patient remained seizure free.